The cis-Regulatory Atlas of the Mouse Immune System

A complete chart of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of differentiation and function of an organ system. We generated matched epigenome and transcriptome measurements in 86 primary cell types that span the mouse immune system and...

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Bibliographic Details
Published in:Cell 2019-02, Vol.176 (4), p.897-912.e20
Main Authors: Yoshida, Hideyuki, Lareau, Caleb A., Ramirez, Ricardo N., Rose, Samuel A., Maier, Barbara, Wroblewska, Aleksandra, Desland, Fiona, Chudnovskiy, Aleksey, Mortha, Arthur, Dominguez, Claudia, Tellier, Julie, Kim, Edy, Dwyer, Dan, Shinton, Susan, Nabekura, Tsukasa, Qi, YiLin, Yu, Bingfei, Robinette, Michelle, Kim, Ki-Wook, Wagers, Amy, Rhoads, Andrew, Nutt, Stephen L., Brown, Brian D., Mostafavi, Sara, Buenrostro, Jason D., Benoist, Christophe
Format: Article
Language:English
Subjects:
Animals
ATAC-seq
Binding Sites - genetics
Chromatin
Chromatin Immunoprecipitation - methods
enhancer
Enhancer Elements, Genetic - genetics
epigenomics
Epigenomics - methods
Gene Expression Regulation - genetics
immune cell differentiation
Immune System - immunology
Immune System - metabolism
Mice
Mice, Inbred C57BL
Promoter Regions, Genetic - genetics
Protein Binding - genetics
Regulatory Elements, Transcriptional - genetics
transcription factor
Transcription Factors - metabolism
Transcriptional regulation
Transcriptome - genetics
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Summary:A complete chart of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of differentiation and function of an organ system. We generated matched epigenome and transcriptome measurements in 86 primary cell types that span the mouse immune system and its differentiation cascades. This breadth of data enable variance components analysis that suggests that genes fall into two distinct classes, controlled by either enhancer- or promoter-driven logic, and multiple regression that connects genes to the enhancers that regulate them. Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility, pinpointing specific cis-regulatory elements where binding of given TFs is likely functionally relevant, validated by chromatin immunoprecipitation sequencing (ChIP-seq). Overall, this cis-regulatory atlas provides a trove of information on transcriptional regulation through immune differentiation and a foundational scaffold to define key regulatory events throughout the immunological genome. [Display omitted] •Atlas of 512,595 cis-regulatory elements active in 86 immunologic cell types•Two classes of loci, controlled by either promoter- or enhancer-driven logic•Inference of enhancer elements that activate each gene across differentiation•Context-specificity of enhancer activation by transcription factors A cis-regulatory map of the mouse immune system illuminates gene expression patterns and regulatory logic across 86 primary cell types and pairs immune transcription factors with cell-type-specific regulatory elements.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2018.12.036